In lung cancer arachidonic acid (AA) is metabolized by cyclooxygenase (COX) enzymes leading to prostaglandin (PG) production. In non-small cell lung cancer (NSCLC) PGE2 is a major product. NSCLC PGE2 levels and proliferation are inhibited by non-steroidal antiinflammatory drugs (NSAIDs) such as aspirin. Proliferation and PGE2 levels are increased by epidermal growth factor (EGF) addition to NSCLC cells. In particular, EGF increases COX-2 mRNA in NSCLC cell lines NCI-H157, H1264 and H1299.In the present period VEGF gene expression studies were conducted. VEGF mRNA was increased by PGE2 and VIP using NSCLC cell line NCI-H157. The order of prostaglandin potency was PGE2 >PGE1 > PGF2 . Also, PGE2 increased the intracellular cAMP. The increase in cAMP and VEGF mRNA caused by PGE2 was reversed by somatostatin but not VIP hybrid, a VIP receptor antagonist. Also, VIP and forskolin increased the cAMP. The increase in cAMP and VEGF mRNA caused by VIP was inhibited by somatostatin and VIPhybrid. These results suggest that functional PGE2 and SRIF receptors are present on NSCLC cells.